28mo | pdb_000028mo

Cryo-EM structure of UBA6-UbDha-UBE2Z trapped ternary complex (singly loaded)

spinqualitylabelsall models 28mo, resolution 3.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 28mo is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.01Å Ligands: ATP, IHP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UBE2Z_HUMAN Catalyzes the covalent attachment of ubiquitin to other proteins (By similarity). Specific substrate for UBA6, not charged with ubiquitin by UBE1. May be involved in apoptosis regulation.[PROSITE-ProRule:PRU00388] Publication Abstract from PubMed Attachment of the ubiquitin-like protein (UBL) FAT10 onto substrates targets them for proteasomal degradation. Like ubiquitin, FAT10 is activated by the E1 enzyme UBA6 then transferred to E2 enzymes, but mechanisms controlling ubiquitin versus FAT10 activation by UBA6 and FAT10 transfer onto E2s remain unclear. Using cryo-EM, we visualise all stages of FAT10 E1-E2 handover: adenylation, thiolation and transthiolation. We find that FAT10 monopolises UBA6 by out-competing ubiquitin for thiolation and blocking the adenylation domain, preventing further UBL recruitment and promoting FAT10 signalling. We profiled UBA6-compatible E2 enzymes and found FAT10 transfer is restricted to a select subset associated with specific cellular pathways. UBE2Z (USE1) showed highest activity followed by UBE2D2, UBE2J2 and UBE2S. Capturing FAT10 or ubiquitin transfer from UBA6 to UBE2Z reveals UBE2Z is highly specialised for FAT10 transfer. It simultaneously engages both FAT10 domains (UBL1 and UBL2) and co-ordinates the metabolite inositol hexakisphosphate (InsP(6)) bound within the UBA6 catalytic domain. This InsP(6) co-ordination extends to other FAT10 compatible E2s. Together, our structural and biochemical analyses reveal regulatory mechanisms underpinning FAT10 activation and transfer. We define principles governing selective FAT10 transfer, highlighting favourable interactions with FAT10 C-terminal domain (UBL2) and stable UBA6 binding, ensuring controlled conjugation onto substrates. Structural determinants for FAT10 activation and transfer from UBA6 to E2 enzymes.,Ellison CJ, Riechmann C, Dalietou EV, Simmons MDR, Dodd EC, Elliott PR Nat Commun. 2026 Aug 13;17(1):9751. doi: 10.1038/s41467-026-76603-3. PMID:42733088 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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